Many patients with chronic kidney disease (CKD) eventually progress to end-stage renal disease (ESRD) and need renal replacement therapy to remove fluid and waste products from their bodies and sustain their lives. Most patients with ESRD needing renal replacement therapy receive hemodialysis, where blood is removed from the circulatory system, cleansed in a hemodialysis machine and then returned to the circulatory system. To facilitate hemodialysis, surgeons create discrete “vascular access sites” that can be used to remove and return blood rapidly from ESRD patients. While major advances have been made in hemodialysis machines themselves and other parts of the hemodialysis process, the creation of durable and reliable vascular access sites has seen only modest improvement and remains the Achilles' heel of renal replacement therapy. Failure to provide suitable vascular sites often results in sickness and death for ESRD patients and places a large burden on health care providers, payers, and public assistance programs worldwide.
Vascular access sites for hemodialysis generally come in three forms: arteriovenous fistulas (AVF), arteriovenous grafts (AVG), and catheters. Each type of access site is susceptible to high rates of failure and complications, as described below.
An AVF is constructed surgically by creating a direct connection between an artery and a vein. A functional AVF created at the wrist between the radial artery and the brachial vein is the longest-lasting and most desirable form of hemodialysis access, with a mean patency of about 3 years. The vein leading away from the connection is called the “outflow” vein. Persistent increases in the overall diameter and lumen diameter of the outflow vein are critical components for an AVF to “mature” and become usable. It is widely believed that the rapid flow of blood in the outflow vein created by the AVF and the WSS exerted on the endothelium of the vein is a major factor in bringing about persistent increases in the overall diameter and lumen diameter of the outflow vein. Unfortunately, approximately 80% of ESRD patients are not eligible for an AVF placement at the wrist, usually due to inadequate vein or artery diameters. For eligible patients where AVF placement is attempted, the site may not be usable without further intervention in about 50%-60% of cases, a problem known as “maturation failure.” Small blood vessel diameter, especially small vein diameter, has been identified as a factor in AVF maturation failure. The rapid appearance of aggressive vein wall scarring known as “intimal hyperplasia” has also been identified as an important factor in AVF maturation failure. Some investigators have postulated that areas of relatively rapid or turbulent blood flow in the vein (with resultant high local WSS) are a major factor in causing vein wall scarring, while other investigators propose that this scarring is caused by areas of relatively slower or oscillating blood flow and relatively low or oscillating WSS. In response, attempts have been made to modulate flow patterns in AVF outflow veins in order to minimize AVF failure rates. Still other investigators have postulated that cyclic stretching of the vein caused by the entry of pulsatile arterial blood may also play a role in the stimulation of intimal hyperplasia and outflow vein obstruction in AVF. At the current time, no method exists which preserves the positive effects of elevated blood speed and WSS that cause persistent increases in the overall diameter and lumen diameter or arteries and veins, while eliminating the negative effects of vein wall scarring and obstruction. Not surprisingly, a patient newly diagnosed with ESRD and in need of hemodialysis has only a 50% chance of having a functional AVF six months after starting hemodialysis. Those patients without a functional AVF must undergo hemodialysis with more costly forms of vascular access and are at a greater risk of complications, sickness, and death.
A second type of vascular access site for hemodialysis is an arteriovenous graft (AVG). An AVG is constructed by placing a segment of synthetic conduit between an artery and vein. Typically, an AVG is constructed in the arm or the leg. A portion of the synthetic conduit is placed immediately under the skin and used for needle access. More patients are eligible for AVGs than AVFs, since veins not visible on the skin surface can be used for outflow, and the rate of early failure is much lower than that for AVFs. Unfortunately, AVGs have a mean primary patency of only about 4-6 months, because aggressive intimal hyperplasia and scarring develops rapidly in the wall of the outflow vein near the connection with the synthetic conduit, thus leading to stenosis and thrombosis. Similar to AVF failure, some investigators have postulated that the rapid and turbulent flow of blood in the outflow vein created by the AVG causes intimal hyperplasia and scarring in the wall of the outflow vein, while other investigators have proposed that this scarring is caused by areas of relatively slower or oscillating blood flow and relatively low or oscillating WSS. Still other investigators have postulated that cyclic stretching of the vein caused by the entry of pulsatile arterial blood into the outflow vein may also play a role in the formation of intimal hyperplasia and outflow vein obstruction in an AVG. Although AVGs are less desirable than AVFs, about 25% of patients dialyze with an AVG, mostly because they are not eligible to receive an AVF.
A third type of vascular access site is a catheter. Patients who are not able to get hemodialysis through an AVF or AVG can have a large catheter inserted in the neck, chest, or leg in order to receive hemodialysis. These catheters often become infected, thus placing the patient at high risk for sepsis and death. Patients with catheter sepsis usually require hospitalization, removal of the catheter, insertion of a temporary catheter, treatment with IV antibiotics, and then placement of a new catheter or other type of access site when the infection has cleared. Catheters are also susceptible to obstruction by thrombus and fibrin build-up around the tip. Hemodialysis catheters have a mean patency of about 6 months and are generally the least desirable form of hemodialysis access. Although catheters are less desirable than AVFs and AVGs, about 20% of patients dialyze with a catheter, mostly because they have not been able to receive a functional AVF or AVG, or are not eligible to receive an AVF or AVG.
The problem of hemodialysis access site failure has received more attention recently as the number of ESRD patients undergoing routine hemodialysis has increased worldwide. In 2004, the Centers for Medicare & Medicaid Services (CMS) announced a “Fistula First” initiative to increase the use of AVFs in providing hemodialysis access for patients with end-stage renal failure. This major initiative is a response to published Medicare data showing that patients who dialyze with an AVF have reduced morbidity and mortality compared to patients with an AVG or a catheter. Costs associated with AVF patients are substantially lower than the costs associated with AVG patients in the first year of dialysis, and in subsequent years. The cost savings of a dialyzing with an AVF are even greater when compared to dialyzing with a catheter.
To be eligible for an AVF, patients generally need to have a peripheral vein with an overall diameter of at least 2.5 mm and a peripheral artery with an overall diameter of at least 2.0 mm, with the understanding that different vascular surgeons will set different threshold levels. To be eligible for an AVG, patients generally need to have a peripheral vein with an overall diameter of at least 4 mm and a peripheral artery with an overall diameter of at least 3.0 mm, with the understanding that different vascular surgeons will set different threshold levels. Currently, there is no method for persistently increasing the overall diameter and lumen diameter of peripheral veins and arteries in ESRD patients who have inadequate initial vein or artery size prior to the creation of an AVF or AVG. Consequently, patients with veins or arteries that are too small to attempt an AVF or AVG must use less desirable forms of vascular access such as catheters. Similarly, there is currently no approved method for the treatment of AVF maturation failure, which falls disproportionately on patients with small vein and artery diameters, such as women and minorities. Thus, there is a desire for systems and methods for enlarging the overall diameter and lumen diameter of a vein or artery prior to the creation of AVF or AVG. A recent study demonstrated that ESRD patients who were forced to use less desirable forms of vascular access such as catheters had a substantially higher risk of becoming sick or dying when compared with patients who were able to use an AVF or AVG for hemodialysis.
There is also a need to persistently increase the vein or artery diameter for patients with atherosclerotic blockages of peripheral or coronary arteries in need of bypass grafting. Patients with peripheral artery disease (PAD), who have an obstruction to blood flow in the arteries of the legs, often suffer from claudication, skin ulceration, and tissue ischemia. Many of these patients may eventually require amputation of portions of the affected limb. In some PAD patients the obstruction can be relieved to an adequate degree by balloon angioplasty or the implantation of a vascular stent. In other patients, however, the obstruction is too severe for these types of minimally invasive therapies. Therefore, surgeons will often create bypass grafts that divert blood around the obstructed arteries and restore adequate blood flow to the affected extremity. However, many patients in need of a peripheral bypass graft cannot use their own veins as bypass conduits due to inadequate vein or artery diameter and are forced to use synthetic conduits made of materials such as expanded polytetrafluoroethylene (ePTFE, e.g. Gore-Tex) or polyethylene terephthalate (PET, e.g. Dacron). Studies have shown that using a patient's own veins as bypass conduits results in better long term patency than using synthetic bypass conduits made from materials such as PTFE, ePTFE, or Dacron. The use of a synthetic bypass conduit increases the risk of stenosis in the artery at the distal end of the graft and thrombosis of the entire conduit, thereby resulting in bypass graft failure and a recurrence or worsening of symptoms. Thus, there is a desire for systems and methods for increasing the overall diameter and lumen diameter of veins prior to the creation of bypass grafts for patients who are ineligible to use their own veins for the creation of a bypass graft due to inadequate vein diameter.
Patients with coronary artery disease (CAD) who have an obstruction to blood flow to their heart often suffer from chest pain, myocardial ischemia, and myocardial infarct and many of these patients eventually die from the disease. In some of these patients, the obstruction can be relieved to an adequate degree by balloon angioplasty or the implantation of a vascular stent. In many patients, however, the obstruction is too severe for these types of minimally invasive therapies. Therefore, surgeons will often create a bypass graft that diverts blood around the obstructed arteries and restores adequate blood flow to the affected regions of the heart, with the internal mammary arteries and the radial arteries as preferred conduits. However, some patients in need of coronary bypass grafts cannot use internal mammary or radial arteries due to inadequate artery diameter and must use peripheral veins. Studies have shown that using a patient's internal mammary and radial arteries as bypass conduits results in better long-term patency than using peripheral vein segments. The use of peripheral veins as bypass grafts increases the risk of stenosis in the graft and thrombosis of the entire conduit, resulting in bypass graft failure and a recurrence or worsening of symptoms. Thus, there is a desire for systems and methods for increasing the overall diameter and lumen diameter of arteries prior to the creation of coronary bypass grafts for patients who are ineligible to use their own arteries for the creation of a bypass graft due to inadequate artery diameter. Furthermore, systems and methods for increasing the overall diameter and lumen diameter of veins prior to the creation of coronary bypass grafts are also desired for patients with small peripheral vein diameters.